What Is a Genetic Susceptibility to Breast Cancer?

A genetic susceptibility to breast cancer is an inherited predisposition that increases the likelihood of developing the disease. While most breast cancer cases are sporadic, occurring by chance from mutations acquired over a lifetime, a portion is linked to genetic factors passed down through families. These inherited gene mutations are present from birth in all of the body’s cells.

This inherited risk increases a person’s lifetime risk above the general population’s but does not guarantee they will develop breast cancer. Environmental and lifestyle factors also play a part in whether a person with a genetic susceptibility ultimately develops the disease.

High-Risk Genes in Breast Cancer

Certain genes act as tumor suppressors, with a primary function to repair DNA damage that occurs during normal cell division. This prevents cells from growing and dividing uncontrollably. Inherited mutations can impair this repair function, leading to an accumulation of genetic errors and an increased risk of cancer.

The primary genes associated with hereditary breast cancer are BRCA1 and BRCA2. A harmful mutation in the BRCA1 gene can elevate a woman’s lifetime risk of developing breast cancer to as high as 65-79%. For BRCA2 mutations, the estimated lifetime risk is around 61-77%. These risks are higher than the approximate 12% lifetime risk for women in the general population.

Mutations in BRCA1 and BRCA2 are inherited in an autosomal dominant pattern, meaning inheriting just one copy of the mutated gene from either parent increases cancer risk. Each child of a parent with one of these mutations has a 50% chance of inheriting it. These mutations are also linked to an increased risk of other cancers, including ovarian, pancreatic, and prostate cancer, as well as male breast cancer.

Other genes contribute to hereditary breast cancer risk. The PALB2 gene works with BRCA2 to repair DNA, and mutations in it are associated with an increase in breast cancer risk. Other genes that confer a moderate risk include ATM and CHEK2. Harmful variants in the TP53 gene are linked to Li-Fraumeni syndrome, a rare disorder that greatly increases the risk of developing several types of cancer, including breast cancer at a young age.

Recognizing Hereditary Cancer Patterns

Certain patterns within a family’s medical history can suggest an inherited genetic susceptibility to breast cancer. Indicators include:

• A breast cancer diagnosis at an early age, often before 50, as sporadic cancers tend to develop later in life.
• Multiple relatives on the same side of the family with breast cancer, especially across generations or in first-degree relatives like a mother, sister, or daughter.
• A family history that includes related cancers such as ovarian, pancreatic, or aggressive prostate cancer.
• A diagnosis of triple-negative breast cancer, which is more commonly associated with BRCA1 mutations.
• A personal or family history of bilateral breast cancer, which is a new tumor in the second breast rather than a spread from the first.
• Male breast cancer in the family, which is a strong indicator of hereditary risk and often linked to BRCA2 mutations.

Genetic Counseling and Testing

For individuals who recognize these patterns in their family, the next step often involves genetic counseling. A genetic counselor assesses a person’s medical and family history to determine the likelihood of a hereditary cancer syndrome. They also discuss the benefits, risks, and limitations of genetic testing.

The counselor explains what the test can reveal and the potential psychological, social, and family implications, allowing the individual to make an informed decision. This conversation helps prepare the person for the potential impact of the results on health choices and family dynamics.

If an individual proceeds, the genetic test is performed on a blood or saliva sample, which is sent to a lab to be analyzed for mutations in a panel of cancer-related genes. The results fall into one of three categories. A positive result means a known pathogenic mutation was identified, confirming a hereditary cancer susceptibility. A negative result indicates no such mutation was found in the tested genes. A third possibility is a “variant of uncertain significance” (VUS), meaning a genetic change was found, but it is not yet known if it increases cancer risk.

Managing Elevated Genetic Risk

A positive result for a pathogenic mutation allows for a personalized medical management plan developed with healthcare providers. These plans focus on early detection or risk reduction and are tailored to the individual’s specific gene mutation, age, family history, and personal preferences.

One primary strategy is enhanced surveillance, which involves more frequent and intensive cancer screenings starting at an earlier age. For breast cancer risk, this may include annual mammograms and breast MRIs. The combination of these imaging techniques provides a more detailed view of the breast tissue, increasing the chances of early detection.

Another approach is chemoprevention, which uses medications like tamoxifen and raloxifene to reduce cancer risk by blocking the effects of estrogen on breast tissue. These are prescribed after a thorough discussion of their potential benefits and side effects.

Risk-reducing surgeries offer the most significant reduction in cancer risk. A prophylactic mastectomy, the surgical removal of one or both breasts, can lower the risk of breast cancer by 90% or more. Similarly, a risk-reducing salpingo-oophorectomy, the removal of the ovaries and fallopian tubes, can decrease the risk of both ovarian and breast cancer. This decision is highly personal and involves careful consideration of factors like age and childbearing plans.